Inhibition of BET selectively eliminates undifferentiated pluripotent stem cells
- Authors
- Im, Jung Hyun; Hwang, Seon In; Kim, Jong-Wan; Park, Soon-Jung; Kang, Kyu-ree; You, Jueng Soo; Kim, Kee Pyo; Moon, Sung-Hwan; Cha, Hyuk-Jin; Chung, Hyung-Min; Schoeler, Hans R.; Hyun, Jung Keun; Han, Dong Wook
- Issue Date
- Apr-2018
- Publisher
- SCIENCE PRESS
- Keywords
- Bromodomain and extraterminal domain (BET); JQ1; Pluripotent stem cells
- Citation
- SCIENCE BULLETIN, v.63, no.8, pp 477 - 487
- Pages
- 11
- Journal Title
- SCIENCE BULLETIN
- Volume
- 63
- Number
- 8
- Start Page
- 477
- End Page
- 487
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69814
- DOI
- 10.1016/j.scib.2018.02.023
- ISSN
- 2095-9273
2095-9281
- Abstract
- Embryonic stem cells (ESCs) maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale enhancers-namely super-enhancers (SEs), on which BRD4, a member of the bromodomain and extraterminal domain (BET) family is highly enriched-could regulate pluripotency-related transcription factors. Moreover, inhibition of BRD4 binding on SEs has been shown to induce the differentiation of ESCs. However, the underlying mechanism of BRD4 inhibition-mediated stem cell differentiation remains elusive. Here we show that both mouse and human ESCs lose their capacity for self-renewal upon treatment with JQ1, a selective inhibitor of BET family including BRD4, with rapid suppression of pluripotency-associated genes. Notably, a high concentration of JQ1 could selectively eliminate ESCs via apoptosis, without affecting the functionality of differentiated somatic cells from ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of pluripotent stem cell-based cell therapy. (C) 2018 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
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